天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (2): 313-321.doi: 10.16333/j.1001-6880.2021.2.016

• 数据研究 • 上一篇    下一篇

基于网络药理学的四君子汤治疗阿尔茨海默病作用机制研究

张运辉1,2,3,周小青1,2*,伍大华1,4,杨梦琳1,2,3,郑彩杏1,2,童天昊1,2   

  1. 1湖南中医药大学;22011数字中医药协同创新,长沙 410208;3重庆三峡医药高等专科学校中医学院,重庆 404120;4湖南省中医药研究院附属医院,长沙 410006
  • 出版日期:2021-02-28 发布日期:2021-03-04
  • 基金资助:
    国家自然科学基金(81373702);国家自然科学基金(81874462)

Study on mechanism of Sijunzi Decoction in treating Alzheimer's disease based on network pharmacology

ZHANG Yun-hui1,2,3,ZHOU Xiao-qing 1,2*,WU Da-hua1,4,YANG Meng-lin1,2,3,ZHENG Cai-xing1,2,TONG Tian-hao1,2   

  1. 1Hunan University of Chinese Medicine;2 2011 Digtal Traditional Chinese Medicine Collaborative Innovation,Changsha 410208,China;
    3Chongqing Three Gorges Medical College of Chinese Medicine,Chongqing 404120,China;4Affiliated Hospital of Hunan Provincial Academy of Traditional Chinese Medicine,Changsha 410006,China

  • Online:2021-02-28 Published:2021-03-04

摘要:

基于网络药理学探讨四君子汤治疗阿尔茨海默病(AD)的作用机制。借助TCMSP数据库及Uniprot数据库筛选出四君子汤有效成分及靶点基因。通过Drugbank、Dis Ge NET和TTD数据库筛选出阿尔茨海默病的靶点基因;成分靶点与疾病靶点映射后使用Cytoscape 3.7.1 软件构建药物有效成分-靶点蛋白相互作用网络,使用String 数据库绘制靶点蛋白-靶点蛋白相互作用网络;对靶点蛋白利用Metascape数据库进行GO分析和 KEGG分析,最后采用荧光实时定量PCR对网络药理学主要分析结果进行验证。分析结果表明,四君子汤主要关联 AD的β淀粉样蛋白聚集、细胞凋亡、炎症反应、氧化应激反应、自噬、胰岛素代谢等;体外实验提示,四君子汤参与调控APP介导的β淀粉样蛋白聚集,Caspase-3、Bcl-2、Bax介导的细胞凋亡,MAOB介导的氧化应激反应,mTOR介导的自噬,以及INSR介导的胰岛素代谢等通路。综上四君子汤治疗AD具有多成分、多靶点的特点,可为进一步研究其作用机制提供依据。

关键词: 四君子汤, 阿尔茨海默病, 网络药理学, 作用机制

Abstract:

To explore the mechanism of Sijunzi Decoction in the treatment of Alzheimer's disease (AD) based on network pharmacology.The effective components and target genes of Sijunzi Decoction were screened by TCMSP da-tabase and Uniprot database.The target genes of Alzheimer's disease were screened by Dragbank,Dis Ge NET and TTD databases.After mapping the component target with the disease target point,Cytoscape 3.7.1 software is used to construct the drug active component-target protein interaction network,and at the same time,the String database is used to draw the target protein-target protein interaction network;The target protein was analyzed by GO and KEGG using Metascape database.Finally,fluorescence real-time quantitative PCR was used to verify the main analysis results of network pharmacology.The results showed that Sijunzi Decoction was mainly associated with β-amyloid aggregation,apoptosis,inflammation,oxidative stress,autophagy,insulin metabolism etc.of AD.In vitro experiment showed that Sijunzi Decoction was involved in the regulation of APP-mediated β-amyloid aggregation,Caspase-3,Bcl-2,and Bax mediated apoptosis,MAOB mediated oxidative stress,mTOR mediated autophagy,and INSR mediated pathways of insulin metabolism.Conclusion demonstrated that Sijunzi Decoction has the characteristics of multi-component and multi-target treatment of AD,and which provided basis for further research on the mechanism of the decoction.

Key words: Sijunzi decoction, Alzheimer's disease, pharmacology, mechanism of action 

中图分类号:  R285.5